A Rotavirus Vaccine for Prophylaxis of Infants Against Rotavirus Gastroenteritis

Abstract

The need for safe and effective vaccines to reduce morbidity and mortality caused by rotavirus gastroenteritis in children is well-known. A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need. An overview of RIX4414 trials in developed and developing settings is presented for 3 selected trials conducted in Finland (pilot study), Latin America (Brazil, Mexico and Venezuela) and Singapore involving 5024 infants. The vaccine was well-tolerated, with no increase in any solicited symptoms as compared with the placebo. After 2 doses, 61-91% of vaccinated infants developed rotavirus-specific IgA antibodies. There was no interference with immunogenicity of coadministered routine pediatric vaccines. Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05). Vaccine efficacy was observed against severe rotavirus gastroenteritis caused by G1 and non-G1 types including the emerging G9 type (P < 0.05) in Latin America. These results show prospects for widespread use of Rotarix to reduce rotavirus disease burden and warrant continued worldwide evaluation.

Mice Develop Effective but Delayed Protective Immune Responses When Immunized as Neonates either Intranasally with Nonliving VP6/LT(R192G) or Orally with Live Rhesus Rotavirus Vaccine Candidates

“…Protection after natural rotavirus infection has been associated with both serum and intestinal rotavirus antibodies (11,18,19,41,65,68). Even though similar associations have been difficult to establish after live virus immunization (69), very recent evidence suggests a strong correlation between the presence of serum rotavirus IgA and protection following immunization with Rotarix, a candidate vaccine that was licensed in Mexico in 2004 (20). Even with this candidate vaccine, however, it is unclear whether antibodies are responsible for protection or their presence merely correlates with the true effectors of protection.…”

Heterogeneity and Temporal Dynamics of Evolution of G1 Human Rotaviruses in a Settled Population

“…Since then, a variety of approaches to the development of effective rotavirus vaccines have been undertaken. Recently, a promising monovalent G1P1A [8] human attenuated vaccine, Rotarix, which is reported to induce good heterotypic protection, has been licensed (20,57). This formulation is derived from the fact that both P1A [8] and G1 specificities are unanimously acknowledged as the most prevalent and ubiquitous (27,59).…”

Segurança, imunogenicidade e eficácia protetora de duas doses da vacina RIX4414 contendo rotavírus atenuado de origem humana

“…In this context, local reactogenicity findings were similar to those from the whole study, but a comparison between children from Brazil, Mexico and Venezuela cannot be currently made because specific data per country are yet to be published. 11,15 No serious vaccine-related adverse experiences were reported in Belém and elsewhere. Although the number of children in the present study was not sufficient to assess the risk of intussusception, data from a large Phase III trial with RIX4414 in 11 Latin American countries and Finland, involving more than 63,000 subjects, clearly ruled out such a risk.…”

“…18,19 The large predominance of G9 serotype makes the study in Belém unique when compared to other trials with RIX4414, where most of isolates were G1. [10][11][12]15 The canine RV strain obtained from the stools of an infant assigned to the placebo group may represent a reassortant between human and animal virus strains, but also raises the hypothesis of an interspecies transmission. 20 Most episodes of RVGE in Belém were caused by G9 serotype and thus provided an opportunity to assess the performance of the vaccine in a setting where a heterologous RV strain was predominant.…”